Impact of Obefazimod Induction Therapy on Histologic and Combined Histologic and Endoscopic Outcomes in Patients With Moderately to Severely Active Ulcerative Colitis: Week 8 Results from the Phase 2b Induction Trial

Background:
Obefazimod is an investigational, oral, once-daily (od), small molecule which enhances expression of microRNA-124 and is currently in phase 3 clinical trials for the treatment of patients with moderately to severely active ulcerative colitis (UC). Obefazimod demonstrated efficacy and safety in patients with UC at week-8 in a placebo-controlled, Phase 2b induction trial and in the subsequent open-label maintenance (OLM) study. Here we present results for effects of obefazimod induction on histologic and combined histologic and endoscopic outcomes at week 8.
Methods:
Patients with a modified Mayo score of 5-9 and a centrally read Mayo endoscopy subscore ≥2 at induction baseline were randomized 1:1:1:1 to receive either obefazimod 25 mg, 50 mg or 100 mg od or placebo. Rectal or sigmoidal biopsies were collected during endoscopy at baseline and week 8 to evaluate treatment effect on histopathology scores utilizing the Geboes Index. Histologic improvement (Geboes histologic score ≤3.1), and histo-endoscopic mucosal improvement (Geboes histologic score ≤3.1 + Mayo endoscopy subscore of 0 or 1 with no friability; HEMI) were evaluated at week 8.
Results:
Of the 252 patients randomized (with a mean age of 41.2 years; 41.3% female; mean UC disease duration of 8.05 years), 188 received obefazimod treatment (mean age, 41.3 years; female, 42.6%; mean UC disease duration, 7.8 years; median modified Mayo score, 7.0; median FCP, 1676 µg/g), and 64 were administered a placebo (mean age, 41.1 years; female, 37.5%; mean UC disease duration, 8.8 years; median modified Mayo score, 7.0; median FCP, 1788 µg/g). The proportion of patients with histologic improvement at week 8 was 43% among obefazimod-treated patients (all doses) and 31% among those receiving placebo. The proportion of patients with endoscopic improvement at week 8 was 35% among obefazimod-treated patients (all doses) and 13% among those receiving placebo. The proportion of obefazimod-treated patients who achieved HEMI at week 8 was greater than placebo-treated patients (27% vs 13%, respectively). Consistently positive histological outcomes were observed when evaluating all 3 obefazimod induction doses individually compared to placebo.
Conclusions:
In this Phase 2b induction trial, patients with moderately to severely active UC treated with obefazimod experienced clinically meaningful improvements in histologic and combined histologic and endoscopic outcomes at week 8.